The main goal of this project is to establish a functional role for gangliosides as multifunctional biomodulators. Studies in this laboratory revealed that gangliosides have profound modulatory effects on protein phosphorylation and dephosphorylation in the central nervous system and in several other tissues such as skeletal muscle. This lipid second messenger-like action is mediated in part through the regulation of two classes of protein kinases, namely, ganglioside-dependent and ganglioside- modulated protein kinases. Preliminary studies revealed that certain sialic acid-containing oligosaccharides derived from gangliosides could enhance the autophosphorylation activity of a ganglioside-stimulated protein kinase. This finding suggests that perturbation of cellular gangliosides may play a role in altering metabolic signal transduction pathways. The mechanisms of intracellular trafficking of gangliosides also were investigated. We found that both skeletal and cardiac muscle contain unique ganglioside-binding proteins. Further characterization of these proteins may provide new information on the biochemistry of cellular gangliosides and perhaps more insights in the pathogenesis of ganglioside-related diseases.